Review
Cell Biology
Irena Smaga
Summary: This review summarizes the current knowledge on the role of myelin-related changes in depression, as well as the relationship among maternal malnutrition, myelination, and depression. The findings suggest that myelin alterations play a significant role in the development of depression.
Review
Neurosciences
Minkyung Kang, Yao Yao
Summary: Oligodendrocytes are crucial cells in the central nervous system responsible for myelinating axons and supporting the function of neurons. The function and development of oligodendrocytes are tightly regulated by various molecules, with laminin playing a significant role in processes such as survival, migration, proliferation, differentiation, and myelination. Understanding the specific molecular targets and signaling pathways in oligodendrocyte biology may have implications for therapeutic interventions in demyelinating diseases.
Article
Neurosciences
Sheng Zhang, Yan Wang, Jie Xu, Bokyung Kim, Wenbin Deng, Fuzheng Guo
Summary: This study reveals the important role of HIF-alpha in developmental myelination, demonstrating its requirement in controlling OPC differentiation for efficient myelination. Contrary to previous beliefs, it was found that HIF-alpha's regulation of CNS myelination is independent of canonical Wnt signaling, and instead involves the HIF-alpha-Sox9 regulatory axis. This discovery represents a shift in understanding the mechanisms of HIF-alpha-regulated CNS myelination from a Wnt-dependent view to a Wnt-independent one.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Assia Tiane, Melissa Schepers, Renzo Riemens, Ben Rombaut, Patrick Vandormael, Veerle Somers, Jos Prickaerts, Niels Hellings, Daniel van den Hove, Tim Vanmierlo
Summary: In this study, researchers identified Id2 and Id4 as targets of DNA methylation during the differentiation of oligodendrocyte precursor cells. Using CRISPR technology, they confirmed that methylation of Id2/Id4 could drive cell differentiation. Furthermore, they found alterations in methylation and gene expression levels of these genes in multiple sclerosis patients compared to controls.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Neurosciences
He Wang, Mengjia Liu, Zhuoyang Ye, Cuihua Zhou, Huiru Bi, Long Wang, Chen Zhang, Hui Fu, Ying Shen, Jian-Jun Yang, Yimin Hu, Guiquan Chen
Summary: This study reveals that the phosphorylation of FoxO1 by Akt plays a critical role in Sox10 expression and OL differentiation. Deletion of all three Akt isoforms leads to downregulation of Sox10, and mutant FoxO1 inhibits Sox10 promoter activity.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Jiajia Wang, Lijun Yang, Mingqing Jiang, Chuntao Zhao, Xuezhao Liu, Kalen Berry, Ari Waisman, Abraham J. Langseth, Bennett G. Novitch, Dwight E. Bergles, Akiko Nishiyama, Q. Richard Lu
Summary: Through multiple experiments, it is shown that Olig2 is essential for the differentiation, myelination, and repair of immature OLs, contrary to previous findings. Additionally, the study highlights the importance of using Cre-dependent reporter genes in studying cell state progression.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Shaline V. Fazal, Clara Mutschler, Civia Z. Chen, Mark Turmaine, Chiung-Ya Chen, Yi-Ping Hsueh, Andrea Ibanez-Grau, Andrea Loreto, Angeles Casillas-Bajo, Hugo Cabedo, Robin J. M. Franklin, Roger A. Barker, Kelly R. Monk, Benjamin J. Steventon, Michael P. Coleman, Jose A. Gomez-Sanchez, Peter Arthur-Farraj
Summary: Since SARM1 mutations have been identified in human neurological disease, inhibiting SARM1 has become an attractive therapeutic strategy to preserve axons. However, it is still unknown whether SARM1 is present and functional in myelinating glia. This study finds that oligodendrocytes express SARM1 and its activation results in cell death, while peripheral glia (Schwann cells) likely contain no functionally relevant levels of SARM1.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Alba Huerga-Gomez, Tania Aguado, Anibal Sanchez-de la Torre, Ana Bernal-Chico, Carlos Matute, Susana Mato, Manuel Guzman, Ismael Galve-Roperh, Javier Palazuelos
Summary: This study demonstrates that acute THC administration in early postnatal mice enhances OL development and CNS myelination by promoting oligodendrocyte precursor cell cycle exit and differentiation, which is mediated by CB1 and CB2 cannabinoid receptors and relies on the activation of the mTORC1 signaling pathway.
Article
Neurosciences
Nataliya Tokarska, Justin M. A. Naniong, Jayne M. Johnston, Hannah E. Salapa, Gillian D. Muir, Michael C. Levin, Bogdan F. Popescu, Valerie M. K. Verge
Summary: Acute intermittent hypoxia (AIH) is a novel and effective therapy for peripheral nerve repair, and this study evaluated its impact on central nervous system repair in the experimental autoimmune encephalomyelitis (EAE) model of Multiple Sclerosis (MS). The results showed that AIH significantly improved functional recovery, reduced tissue damage and inflammation, and promoted remyelination and recruitment of precursor cells. This suggests that AIH could be a promising non-invasive therapy for enhancing central nervous system repair and altering the disease course of demyelination in MS.
Article
Developmental Biology
Jing An, Yumeng Zhang, Alexander D. Fudge, Haixia Lu, William D. Richardson, Huiliang Li
Summary: GPR37L1 is expressed in subsets of OL precursors and newly formed immature OLs in the adult mouse brain, and knockout of Gpr37l1 gene inhibits OP proliferation and differentiation, leading to a reduction in the number of adult-born OLs. This suggests that GPR37L1 may play a role in adult OL generation and adaptive myelination.
DEVELOPMENTAL NEUROBIOLOGY
(2021)
Article
Cell Biology
Yuki Miyamoto, Tomohiro Torii, Miho Terao, Shuji Takada, Akito Tanoue, Hironori Katoh, Junji Yamauchi
Summary: In mice, the atypical Rho family GTPase Rnd2 plays biphasic roles in oligodendrocyte myelination, promoting myelination in the early period and inhibiting myelination in the later period. This unique modulator thus exhibits different effects depending on the stage of myelination.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Review
Biochemistry & Molecular Biology
Shunqi Wang, Yingxing Wang, Suqi Zou
Summary: This article reviews the process of oligodendrocyte myelination and its regulatory factors, including proliferation, differentiation, and factors influencing myelination.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lingyu Shi, Zongyi Wang, Yujiao Li, Zheng Song, Wu Yin, Bing Hu
Summary: This study reveals the critical role of chd7 in oligodendrocyte migration and myelination in zebrafish, potentially associated with CHARGE syndrome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Ruyi Mei, Linyu Huang, Mengyuan Wu, Chunxia Jiang, Aifen Yang, Huaping Tao, Kang Zheng, Junlin Yang, Wanhua Shen, Xianjun Chen, Xiaofeng Zhao, Mengsheng Qiu
Summary: Itpr2 plays a crucial role in the developmental process of oligodendrocytes, with its deficiency leading to increased myelination of small-diameter axons by oligodendrocytes, hence affecting the normal functioning of the nervous system.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Jun Zhang, Jian-guang Sun, Xiaowen Xing, Rong Wu, Lujun Zhou, Ying Zhang, Fang Yuan, Shukun Wang, Zengqiang Yuan
Summary: In both developmental myelination and remyelination in the central nervous system, the c-Abl kinase plays a crucial role in the proliferation of OL progenitor cells by directly phosphorylating the transcription factor Olig2. Lack of c-Abl results in insufficient OPC proliferation and reduced expression of myelin-related genes, leading to impaired myelination.
Article
Psychology, Developmental
Jesminne Castricum, Joke H. M. Tulen, Walter Taal, Andre B. Rietman, Ype Elgersma
Summary: In this study, adults with NF1 performed similarly to controls in attention and motor learning tasks, with the only difference being shorter reaction times in controls. Measures of attention or motor learning were not significantly associated with reduced intellectual performance in NF1. These findings contrast with previous studies in children with NF1 and suggest potential differences in cognitive functioning between pediatric and adult NF1 populations.
JOURNAL OF ATTENTION DISORDERS
(2022)
Article
Biochemistry & Molecular Biology
Martina Proietti Onori, Linda M. C. Koene, Carmen B. Schaefer, Mark Nellist, Marcel de Brito van Velze, Zhenyu Gao, Ype Elgersma, Geeske M. van Woerden
Summary: The study utilized a mouse model expressing RHEBp.P37L in the somatosensory cortex to uncover the mechanism underlying epilepsy caused by mTOR pathway hyperactivation, revealing that enhanced axonal connectivity leads to hyperexcitability in distal neurons. Blocking axonal vesicle release from RHEBp.P37L neurons alone effectively stopped seizures and normalized the hyperexcitability of distant neurons.
Article
Genetics & Heredity
Sarah C. Borrie, Ellen Plasschaert, Zsuzsanna Callaerts-Vegh, Akihiko Yoshimura, Rudi D'Hooge, Ype Elgersma, Steven A. Kushner, Eric Legius, Hilde Brems
Summary: The study found that Spred1-/- mice exhibit changes in social and communicative behaviors, and pharmacological targeting of the Ras-MAPK pathway can reverse these behavioral phenotypes. Through research on mouse models, it was revealed that dysregulation of the Ras-MAPK signaling pathway plays a key role in mediating social behavior phenotypes in ASD mouse models.
Article
Medicine, Research & Experimental
Claudia Milazzo, Edwin J. Mientjes, Ilse Wallaard, Soren Vestergaard Rasmussen, Kamille Dumong Erichsen, Tejaswini Kakunuri, A. S. Elise van der Sman, Thomas Kremer, Meghan T. Miller, Marius C. Hoener, Ype Elgersma
Summary: Research findings demonstrate that ASO-induced reactivation of UBE3A in AS mice can lead to positive effects on AS phenotypes, such as restored sensitivity to seizures and improvements in behavior, indicating therapeutic potential.
Article
Psychiatry
Jesminne Castricum, Tom K. Birkenhager, Steven A. Kushner, Ype Elgersma, Joke H. M. Tulen
Summary: This study investigated inhibitory neurotransmission and cortical plasticity in MDD patients and controls using TMS technology, finding deficits in cortical plasticity in MDD patients. However, no significant differences in cortical inhibition were observed in depressed patients, suggesting that reduced cortical inhibition may not be a robust correlate of the pathophysiological mechanism in MDD.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Medicine, Research & Experimental
Linda Mc Koene, Eva Niggl, Ilse Wallaard, Martina Proietti-Onori, Diana C. Rotaru, Ype Elgersma
Summary: The study utilized an inducible Tsc1-knockout mouse model to examine the electrophysiological and molecular changes during Tsc1-induced epileptogenesis. Deletion of Tsc1 led to hippocampus-specific changes in excitability and adaptation, which were rescued by early treatment with the mTOR inhibitor rapamycin. Transcriptome analysis revealed significant transcriptional changes during epileptogenesis, with the potential involvement of ion channels in driving epileptogenesis. These findings suggest that targeting the TSC/mTOR signaling pathway may be a promising therapeutic approach for epilepsy in individuals with TSC.
Article
Medicine, Research & Experimental
Matthew C. Judson, Charles Shyng, Jeremy M. Simon, Courtney R. Davis, A. Mattijs Punt, Mirabel T. Salmon, Noah W. Miller, Kimberly D. Ritola, Ype Elgersma, David G. Amaral, Steven J. Gray, Benjamin D. Philpot
Summary: Loss of maternal UBE3A allele leads to Angelman syndrome (AS), a severe neurodevelopmental disorder. Reinstating dual-isoform expression of human UBE3A in the developing brain through gene transfer significantly improved motor learning and innate behaviors in AS mice, demonstrating the therapeutic potential of this approach.
Review
Genetics & Heredity
F. Isabella Zampeta, Ben Distel, Ype Elgersma, Rik Iping
Summary: This study reviews the development of Angelman syndrome research over the past 50 years using a bibliometric approach. The results reveal a shift in research focus towards genetic therapies for Angelman syndrome and provide insights into changes in funding sources, publishing journals, and international collaborations.
Article
Biochemistry & Molecular Biology
Nikhil J. Pandya, Sonja Meier, Stefka Tyanova, Marco Terrigno, Congwei Wang, A. Mattijs Punt, E. J. Mientjes, Audrey Vautheny, Ben Distel, Thomas Kremer, Ype Elgersma, Ravi Jagasia
Summary: This study investigates the mechanisms and potential therapeutic options for Angelman syndrome. Proteomics analysis reveals changes in protein pathways during different stages of development in an AS mouse model. Restoring UBE3A expression is shown to reverse these changes and provide a promising treatment option. Additionally, a novel UBE3A substrate is discovered, and a protein database is created to support future research.
MOLECULAR PSYCHIATRY
(2022)
Article
Neurosciences
Lucas Wahl, A. Mattijs Punt, Tara Arbab, Ingo Willuhn, Ype Elgersma, Aleksandra Badura
Summary: The marble burying test is commonly used to describe behaviors in mouse models of neurodevelopmental and psychiatric disorders. A new automated method using machine learning algorithms was introduced to quantify burying behavior in freely moving mice. The accuracy of the method was confirmed in three mouse models, showing consistent results with previously reported phenotypes. The study also revealed additional information about mouse activity during the test.
Article
Genetics & Heredity
Geeske M. van Woerden, Richelle Senden, Charlotte de Konink, Rossella A. Trezza, Anwar Baban, Jennifer A. Bassetti, Yolande van Bever, Lynne M. Bird, Bregje W. van Bon, Alice S. Brooks, Qiaoning Guan, Eric W. Klee, Carlo Marcelis, Joel M. Rosado, Lisa A. Schimmenti, Amy R. Shikany, Paulien A. Terhal, Kathryn Nicole Weaver, Marja W. Wessels, Hester van Wieringen, Anna C. Hurst, Catherine F. Gooch, Katharina Steindl, Pascal Joset, Anita Rauch, Marco Tartaglia, Marcello Niceta, Ype Elgersma, Serwet Demirdas
Summary: This study identifies clinical phenotypes associated with MAP3K7 gene mutations, confirming the correlation between different mutation types and phenotypes in FMD2 and CSCF, and highlighting the importance of considering MAP3K7 mutations in the differential diagnosis of cardiac defects, connective tissue disorders, and NS.
Article
Psychiatry
Joseph K. Tanas, Devante D. Kerr, Li Wang, Anika Rai, Ilse Wallaard, Ype Elgersma, Michael S. Sidorov
Summary: Angelman syndrome (AS) is a neurodevelopmental disorder that affects motor function, cognition, and sleep, among other comorbidities. Multidimensional analysis has been used to quantify the behavioral profiles of AS mice, accurately predicting their genotype and evaluating the effectiveness of treatment.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Medicine, Research & Experimental
A. Mattijs Punt, Matthew C. Judson, Michael S. Sidorov, Brittany N. Williams, Naomi S. Johnson, Sabine Belder, Dion den Hertog, Courtney R. Davis, Maximillian S. Feygin, Patrick F. Lang, Mehrnoush Aghadavoud Jolfaei, Patrick J. Curran, Wilfred F. J. van Ijcken, Ype Elgersma, Benjamin D. Philpot
Summary: Chromosome 15q11.2-q13.1 duplication syndrome (Dup15q syndrome) is a severe neurodevelopmental disorder characterized by intellectual disability, impaired motor coordination, and autism spectrum disorder. While overexpression of the UBE3A gene is presumed to be the main cause of Dup15q pathology, studies on mouse models with UBE3A overexpression have yielded conflicting results. In this study, transgenic mouse models were used to investigate the neurodevelopmental impact of Ube3a gene overdosage and found limited effects on neurodevelopment, but increased mortality when faced with seizures.
Meeting Abstract
Biochemistry & Molecular Biology
A. Aartsma-Rus, M. Lauffer, R. Collin, Y. Elgersma, W. van Roon-Mom
Article
Genetics & Heredity
Inge den Besten, Rianne F. de Jong, Amber Geerts-Haages, Hennie T. Bruggenwirth, Marije Koopmans, Alice Brooks, Ype Elgersma, Dederieke A. M. Festen, Marlies J. Valstar
Summary: This study describes the clinical phenotypes of Angelman syndrome (AS) in adults, revealing significant health issues such as constipation, reflux, visual problems, scoliosis, behavioral problems, and sleeping problems. Epilepsy was reported in 57% of adults with AS, impacting their level of functioning. A decline in mobility was noted in the majority of adults, with a minority showing microcephaly.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
